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Early hemodynamic resuscitation in septic shock: understanding and modifying oxygen delivery


In a previous issue of Critical Care, researchers have focused on the venous-to-arterial carbon dioxide difference (Pv-aCO2) as a surrogate marker for systemic perfusion in patients with septic shock. Although the complex mechanisms responsible for an increased Pv-aCO2 in septic shock need to be further unraveled, the potential prognostic value of Pv-aCO2 seems clinically relevant and useful in daily practice in view of its easy availability.

The resuscitation of patients with sepsis remains a challenging task. In the presence of shock, early optimization of global and regional perfusion mandates adequate monitoring. Whatever kind of monitoring is used, it should provide reliable information with potential therapeutic and prognostic relevance. In a previous issue of Critical Care, Ospina-Tascón and colleagues [1] describe a potentially useful tool as a target for resuscitating early septic shock. The Surviving Sepsis Campaign guidelines for early hemodynamic optimization recommend normalization of central venous oxygen saturation (ScvO2) [2]. ScvO2 reflects the imbalance between oxygen delivery (DO2) and oxygen demand (VO2). However, in the majority of patients with severe sepsis or septic shock who are acutely admitted to the ICU, ScvO2 values are normal or elevated (>70%) [3]. Hence, an additional circulatory parameter is needed to evaluate resuscitation efforts.

Ospina-Tascón and colleagues [1] have focused on the venous-to-arterial carbon dioxide difference (Pv-aCO2) as a surrogate marker for systemic perfusion in patients with septic shock. This could make sense. Indeed, Pv-aCO2 may be used to mathematically calculate cardiac index [4]. In addition, a cutoff value for Pv-aCO2 of 6 mm Hg may be used to discriminate between high and low lactate clearance and cardiac index in critically ill patients who were seemingly resuscitated [5].

In a prospective observational study, Ospina-Tascón and colleagues [1] classify their patient population into four predefined groups based on the evolution of Pv-aCO2 during the first 6 hours of resuscitation. A Pv-aCO2 of at least 6 mm Hg was considered high (H), and a Pv-aCO2 of less than 6 mm Hg was considered normal or low (L). Their results show that two groups have better outcome: that is, patients with low Pv-aCO2 throughout the observational period (LL) and patients in whom Pv-aCO2 decreased from high to low values (HL) [1]. The patients in the first group were either less severely ill or already adequately volume-resuscitated before ICU admission. Analogously to earlier findings [5], the HL patients may be considered responders to treatment mirrored by the significant lactate clearance from 2.7 to 1.3 mmol/L. In contrast, persistently high Pv-aCO2 values (HH) or increasing Pv-aCO2 values (LH) predicted worse outcome. The patients in the HH group were too severely ill, and during treatment for the patients in the LH group a substantial oxygen debt was probably recognized too late. In addition, an increased mortality risk was observed when patients reached an ScvO2 of at least 70 % with concomitantly high Pv-aCO2 values. This is in line with recent findings that Pv-aCO2 may be used as triage tool when ScvO2 values are more than 70% on ICU admission [5,6]. Hence, Pv-aCO2 may potentially be of prognostic value. In addition, Pv-aCO2 values can be easily obtained with low costs, making this parameter potentially clinically relevant and useful in daily practice.

Nevertheless, one has to bear in mind that the mechanisms responsible for an increased Pv-aCO2 in patients with septic shock are not fully understood yet. On the microcirculatory level, distributive changes may be independent of cardiac output (CO) [7]. This means that on a regional level, in accordance with the possibility of persistent hypoxia despite normal ScvO2 levels, the accumulation of carbon dioxide (CO2) occurs in microcirculatory weak units, despite adequate CO. However, Pv-aCO2 reflects the ability to wash out the accumulated CO2 better than the presence of anaerobic metabolism [7,8]. Also, an increased Pv-aCO2-to-VO2 ratio could reflect global anaerobic metabolism [9], and the ratio of Pv-aCO2 divided by arteriovenous oxygen content difference predicts an increase of oxygen utilization after a fluid-induced increase in DO2 [10]. This means that Pv-aCO2 values may also be of therapeutic relevance. A decrease of heterogeneity of the microcirculation may potentially result in an increased CO2 washout and a decreased Pv-aCO2-to-VO2 ratio. Also, the balance between DO2 and VO2 may be restored. It is tempting to hypothesize that the necessary improved recruitment of microcirculation in the early resuscitation phase may be achieved by the use of vasodilatators in addition to volume loading [11,12]. Indeed, the results of Ospina-Tascón and colleagues may provide an argument to implement vasodilators within 6 hours, which probably could be stopped after recruitment has occurred. Such a strategy may be particularly beneficial to septic shock patients resembling the patients described in the LH group.

In conclusion, Pv-aCO2 provides us with additional information to hemodynamic and oxygen-derived parameters currently used in the resuscitation of patients with sepsis. Pv-aCO2 values seem clinically relevant and are potentially of prognostic value.



Cardiac output


Carbon dioxide


Oxygen delivery

HH group:

Patients with persistently high venous-to-arterial carbon dioxide difference values

HL group:

Patients with decreasing venous-to-arterial carbon dioxide difference values

LH group:

Patients with increasing venous-to-arterial carbon dioxide difference values

LL group:

Patients with persistently low venous-to-arterial carbon dioxide difference values


Venous-to-arterial carbon dioxide difference


Central venous oxygen saturation


Oxygen demand.


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Correspondence to Paul A van Beest.

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van Beest, P.A., Spronk, P.E. Early hemodynamic resuscitation in septic shock: understanding and modifying oxygen delivery. Crit Care 18, 111 (2014).

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